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Background and aims Although smoking cessation medications have shown effectiveness in increasing abstinence in randomized controlled trials (RCTs), it is unclear to what extent benefits persist over time. This paper assesses whether the benefits of smoking cessation medications decline over the first year. Methods We selected studies from three systematic reviews published by the Cochrane Collaboration. RCTs of first‐line smoking cessation medications, with 6‐ and 12‐month follow‐up, were eligible for inclusion. Meta‐analysis was used to synthesize information on sustained abstinence (SA) at 6 versus 12 months and 3 versus 6 months, using the risk difference (RD) (‘net benefit’) between intervention and control group quit rates, the relative risk (RR) and the odds ratio (OR). Results Sixty‐one studies (27 647 participants) were included. Fewer than 40% of intervention group participants were sustained abstinent at 3 months (bupropion: 37.1%; nicotine replacement therapy (NRT): 34.8%; varenicline: 39.3%); approximately a quarter were sustained abstinent at 6 months (bupropion: 25.9%; NRT: 26.6%; varenicline: 25.4%), and approximately a fifth were sustained abstinent at 12 months (bupropion: 19.9%; NRT: 19.8%%; varenicline: 18.7%). There was only a small decline in RR (3 months: 1.95 [95% confidence interval (CI) = 1.74–2.18, P

Smoking cessation medications (SCMs) are an evidence-based cornerstone of comprehensive tobacco control programs globally. However, the impact of SCMs on population smoking prevalence is controversial, with inconsistencies between randomized controlled trials (RCTs) and population-based observational studies. We estimated SCM impact on permanent cessation and population smoking prevalence by extrapolating efficacy estimates from meta-analyses of RCTs, using the standard population impact formula: efficacy*reach. We calculated the potential SCM impact under a range of assumptions for permanent cessation (20%,14%), behavioral support (yes/no), reach (40%-2%), and underlying smoking prevalence. Assuming behavioral support for all, depending on reach, 8%-0.3% of smokers are expected to quit permanently. Without behavioral support, permanent cessation is estimated to be 6.4%-0.2%. Assuming an underlying population smoking prevalence of 14%, (current U.S. prevalence), the maximum impact on population smoking prevalence is 1.12%. Impact on prevalence increases with increasing underlying country-specific levels of prevalence. With current U.S. levels of reach, behavioral support and smoking prevalence, we estimate that, based on a single course of treatment, 2.3% of smokers would quit permanently, contributing to a 0.3% decrease in population level smoking prevalence. Even under ideal conditions, the potential of current first-line SCMs to increase cessation in a substantial proportion of smokers, and reduce population smoking prevalence, is limited. In order to avert the predicted billion tobacco-caused deaths in this century, "safe and effective" medications are not sufficient: SCMs with high population impact are urgently needed. Policies to ensure the availability and accessibility of highly efficacious SCMs, with behavioral support, are crucial.

Summary Successful fracture repair requires restoration of bone morphology and mechanical integrity. Recent evidence shows that fractured bones of neonatal mice undergo spontaneous realignment, dubbed “natural reduction.” Here, we show that natural reduction is regulated by the proprioceptive system and improves with age. Comparison among mice of different ages revealed, surprisingly, that 3-month-old mice exhibited more rapid and effective natural reduction than newborns. Fractured bones of null mutants for transcription factor Runx3, lacking functional proprioceptors, failed to realign properly. Blocking Runx3 expression in the peripheral nervous system, but not in limb mesenchyme, recapitulated the null phenotype, as did inactivation of muscles flanking the fracture site. Egr3 knockout mice, which lack muscle spindles but not Golgi tendon organs, displayed a less severe phenotype, suggesting that both receptor types, as well as muscle contraction, are required for this regulatory mechanism. These findings uncover a physiological role for proprioception in non-autonomous regulation of skeletal integrity., Graphical Abstract, Highlights • Realignment of fractured bones fails in mice lacking proprioceptive receptors • Realignment is more rapid and effective in 3-month-old mice than in newborns • Muscle contraction is also required for proper natural reduction • These findings reveal a key role for proprioception in regulating fracture repair, Blecher et al. report that natural reduction, the process whereby fractured bones are realigned, fails in mutant mice lacking functional proprioceptive circuitry. Surprisingly, natural reduction was more rapid and effective in 3-month-old mice than in newborns. These findings suggest a physiological role for proprioception in non-autonomous regulation of skeletal integrity.

Disability scales do not enable the transmission of concise, meaningful and daily function description for clinical purposes. Cross-sectional statistical analysis of 328 patients’ Spinal Cord Independence Measure (SCIM) III item scores (SIS). To develop a concise and clinically interpretable data-based characterization of daily task accomplishment for patients with spinal cord lesions (SCLs). Multi-center study at 13 spinal units in 6 countries. Patients were grouped into clusters characterized by smaller differences between the patients’ SIS within the clusters than between their centers, using the k-medoides algorithm. The number of clusters (k) was chosen according to the percent of SIS variation they explained and the clinical distinction between them. Analysis showed that k=8 SIS clusters offer a good description of the patient population. The eight functional clusters were designated as A–H, each cluster (grade) representing a combination of task accomplishments. Higher grades were usually (but not always) associated with patients implementing more difficult tasks. Throughout rehabilitation, the patients’ functional grade improved and the distribution of patients with similar functional grades within the total SCIM III score deciles remained stable. A new classification based on SIS clusters enables a concise description of overall functioning and task accomplishment distribution in patients with SCL. A software tool is used to identify the patients’ functional grade. Findings support the stability and utility of the grades for characterizing the patients’ functional status.

Background. A quadratic formula of the Spinal Cord Injury Ability Realization Measurement Index (SCI-ARMI) has previously been published. This formula was based on a model of Spinal Cord Independence Measure (SCIM95), the 95th percentile of the SCIM III values, which correspond with the American Spinal Injury Association Motor Scores (AMS) of SCI patients. Objective. To further develop the original formula. Setting. Spinal cord injury centers from 6 countries and the Statistical Laboratory, Tel-Aviv University, Israel. Methods. SCIM95 of 661 SCI patients was modeled, using a quantile regression with or without adjustment for age and gender, to calculate SCI-ARMI values. SCI-ARMI gain during rehabilitation and its correlations were examined. Results. A new quadratic SCIM95 model was created. This resembled the previously published model, which yielded similar SCIM95 values in all the countries, after adjustment for age and gender. Without this adjustment, however, only 86% of the non-Israeli SCIM III observations were lower than those SCIM95 values ( P < .0001). Adding the variables age and gender to the new model affected the SCIM95 value significantly ( P < .04). Adding country information did not add a significant effect ( P > .1). SCI-ARMI gain was positive (38.8 ± 22 points, P < .0001) and correlated weakly with admission age and AMS. Conclusions. The original quadratic SCI-ARMI formula is valid for an international population after adjustment for age and gender. The new formula considers more factors that affect functional ability following SCI.

The spinal cord injury ability realization measurement index (SCI-ARMI) assesses rehabilitation potential and efficacy based on the linear relationship between the Spinal Cord Independence Measure (SCIM) and the American Spinal Injury Association impairment scale (AIS) motor scores (AMS). The objective of this study is to develop new SCI-ARMI formulas using a more flexible approach that is less sensitive to the distribution of the AMS score among spinal cord lesion (SCL) patients. Loewenstein Rehabilitation Hospital, Raanana, and the Statistical Laboratory, School of Mathematics, Faculty of Exact Sciences, Tel-Aviv University, Israel. SCIM III and AMS of 226 Israeli SCL patients were monitored. Linear formulas, quadratic formulas and non-parametric formulas were estimated to express the relationship between the 95th percentile of the SCIM III values for patients with given AMS at discharge from rehabilitation (SCIM95) and the corresponding AMS value. This relationship was used to calculate SCI-ARMI values, defined as the ratio of the observed SCIM score and the respective SCIM95 for a given patient's AMS score. The estimated quadratic formula for the relationship between the 95th percentile of the SCIM III and the AMS score was found to be most appropriate, and formulas are provided for SCIM95 calculation in the various areas of function. The use of these formulas to calculate SCI-ARMI values is presented. The new formulas improve the accuracy of calculated ability realization for any AMS. The new statistical procedure will be used for the upcoming data analysis of a larger-scale international SCI-ARMI study.